PROJECT SUMMARY In response to RFA-OD-16-004, our overarching goal is to determine the early life ?exposome?, across a wide range of exposures (social, lifestyle, nutritional, chemical, physical), and conduct integrative analyses with child health outcomes that are informed by biological pathways and account for postnatal factors. We propose to leverage an existing, ongoing pre-birth cohort in Colorado, Healthy Start, which has recruited and is currently following 1410 mother-child dyads up to age 4-5 years (R01DK076648, PI Dabelea). Biological samples have been collected during pregnancy, at birth, and are now being obtained at age 4-5 years. Our study proposes to leverage this cohort by accomplishing the following aims: AIM 1: Expand the assessment of prenatal and early life environmental exposures (air pollution, built environment) and add to exposures already measured (social, lifestyle, nutritional, chemical) to define exposure patterns (external domain of the exposome); AIM 2: Measure biological signatures (internal domain of the exposome) associated with prenatal environmental exposures in subsets of children with available samples (cord blood, umbilical-derived mesenchymal stem cells, and placentas); AIM 3: Continue the longitudinal follow up of the cohort to age 7-8 years focusing on obesity, vascular, metabolic, neurocognitive and respiratory outcomes, as well as postnatal social and behavioral factors; AIM4: Conduct integrative analyses to assess the relationships of multiple and combined early life exposures with child outcomes. Biological, social and behavioral pathways and mediators will be explored. Our study is poised to integrate estimates of already available and newly measured environmental exposures operating during prenatal/early life, together with their biological signatures and likely effects on developmental behaviors, to provide a first step in the much needed holistic understanding of the etiology of childhood chronic diseases. By continuing to longitudinally follow up the Colorado Healthy Start cohort and collaborating with the larger ECHO consortium we will be able to expand the scope of our work, by refining and incorporating additional components of the exposome, exploring changes in the composition and impact of the exposome over time, targeting additional childhood outcomes, and participating in large gene-environment interaction studies.